Copper Cu 64-DOTA-Trastuzumab PET in Predicting Response to Treatment With Ado-Trastuzumab Emtansine in Patients With Metastatic HER2 Positive Breast Cancer

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2014 by City of Hope Medical Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT02226276
First received: August 25, 2014
Last updated: August 25, 2014
Last verified: August 2014
  Purpose

This pilot clinical trial studies how well copper Cu 64-tetra-azacyclododecanetetra-acetic acid (DOTA)-trastuzumab positron emission tomography (PET) works in predicting response to treatment with ado-trastuzumab emtansine in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer that has spread to other places in the body. Diagnostic procedures, such as copper Cu 64-DOTA-trastuzumab PET, may allow scanners to create images of where it travels in the body and may help doctors identify which patients may benefit from treatment with ado-trastuzumab emtansine.


Condition Intervention
Bone Metastases
HER2-positive Breast Cancer
Liver Metastases
Lung Metastases
Recurrent Breast Cancer
Soft Tissue Metastases
Stage IV Breast Cancer
Radiation: fludeoxyglucose F 18
Procedure: positron emission tomography
Procedure: computed tomography
Biological: trastuzumab
Radiation: copper Cu 64-DOTA-trastuzumab
Biological: ado-trastuzumab emtansine
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: A Pilot Study of 64Cu-DOTA-trastuzumab Positron Emission Tomography in Treatment of Advanced HER2 Positive Breast Cancer With the Antibody Drug Conjugate Ado-trastuzumab Emtansine

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Tumor uptake of copper Cu 64-DOTA-trastuzumab as measured by PET [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Will be correlated with subsequent tumor response to ado-trastuzumab emtansine using a t-test with a 0.05 two-sided significance level.

  • Metabolic tumor response to ado-trastuzumab emtansine as assessed by fludeoxyglucose F 18 PET/CT [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Will be correlated with uptake of copper Cu 64-DOTA-trastuzumab using a t-test with a 0.05 two-sided significance level.

  • Copper Cu 64-DOTA-trastuzumab uptake metrics [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Will be compared between "responding" and "non-responding" tumors using a t-test with 0.05 one-sided significance level.

  • Presence of putative MMRs to ado-trastuzumab emtansine [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Tissue samples will be used to explore the correlation between the presence of MMRs as assessed by histopathology and tumor response to ado-trastuzumab emtansine both in univariate analysis and in combination with tumor uptake of copper Cu 64-DOTA-trastuzumab as measured with PET/CT


Estimated Enrollment: 10
Study Start Date: December 2014
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Diagnostic (copper Cu 64-DOTA-trastuzumab PET)
Patients undergo whole body fludeoxyglucose F 18 PET/CT. Patients then receive trastuzumab IV over 90 minutes immediately before receiving copper Cu 64-DOTA-trastuzumab IV and then undergo PET scans at 24 and 48 hours. Patients then receive ado-trastuzumab emtansine IV every 3 weeks until complete response or disease progression at the discretion of the treating oncologist. Patients undergo restaging by whole body fludeoxyglucose F 18 PET/CT every 6 weeks after initiation of treatment until disease progression.
Radiation: fludeoxyglucose F 18
Undergo fludeoxyglucose F 18 PET/CT
Other Names:
  • 18FDG
  • FDG
Procedure: positron emission tomography
Undergo fludeoxyglucose F 18 PET/CT
Other Names:
  • FDG-PET
  • PET
  • PET scan
  • tomography, emission computed
Procedure: computed tomography
Undergo fludeoxyglucose F 18 PET/CT
Other Name: tomography, computed
Biological: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • Herceptin
  • MOAB HER2
Radiation: copper Cu 64-DOTA-trastuzumab
Given IV
Other Name: 64Cu-DOTA-trastuzumab
Procedure: positron emission tomography
Undergo copper Cu-DOTA-trastuzumab PET
Other Names:
  • FDG-PET
  • PET
  • PET scan
  • tomography, emission computed
Biological: ado-trastuzumab emtansine
Given IV
Other Names:
  • Kadcyla
  • T-DM1
  • trastuzumab-DM1
  • trastuzumab-MCC-DM1
  • trastuzumab-MCC-DM1 antibody-drug conjugate
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Correlate uptake of 64Cu-DOTA-trastuzumab (copper Cu 64-DOTA-trastuzumab) PET by individual tumors with subsequent tumor response to ado-trastuzumab emtansine as assessed by serial 18F-fludeoxyglucose (FDG) (fludeoxyglucose F 18)/PET-computed tomography (CT).

II. Compare tumor uptake of 64Cu-DOTA-trastuzumab PET between patients who do and patients who do not respond to ado-trastuzumab emtansine.

III. Obtain tumor tissue for subsequent assessment of the presence of putative molecular mechanisms of resistance (MMRs) to ado-trastuzumab emtansine. When funding becomes available, those samples will be used to explore the correlation between the presence of MMRs as assessed by histopathology and tumor response to ado-trastuzumab emtansine both in univariate analysis and in combination with tumor uptake of 64Cu-DOTA-trastuzumab as measured with PET/CT.

OUTLINE:

Patients undergo whole body fludeoxyglucose F 18 PET/CT. Patients then receive trastuzumab intravenously (IV) over 90 minutes immediately before receiving copper Cu 64-DOTA-trastuzumab IV and then undergo PET scans at 24 and 48 hours. Patients then receive ado-trastuzumab emtansine IV every 3 weeks until complete response or disease progression at the discretion of the treating oncologist. Patients undergo restaging by whole body fludeoxyglucose F 18 PET/CT every 6 weeks after initiation of treatment until disease progression.

After completion of study treatment, patients are followed up for 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women with metastatic HER2-positive breast cancers whose disease has progressed on first-line trastuzumab + chemotherapy will be considered eligible for study participation if they meet the following criteria:
  • Participants must be women who have histological confirmation of metastatic invasive breast cancer that has metastasized outside the region of the primary tumor and axilla; biopsy must be obtained within 28 days prior to enrollment; patients must have metastatic disease in lung, liver, soft-tissue or bone to qualify for the study (more than one site is permissible)
  • At least 1 site of metastasis >= 20 mm in mean diameter must be identified
  • The cancer must over express HER2 as determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH)
  • Patients may not have received trastuzumab within 6 weeks of projected 64Cu-DOTA-trastuzumab/PET-CT
  • Participants must have normal cardiac ejection fraction
  • Planned therapy with ado-trastuzumab emtansine
  • Ability to provide informed consent
  • Patients that may need dose reduction to commence cycle 1 treatment

Exclusion Criteria:

  • Participants who have received trastuzumab within the prior 30 days
  • Participants who are not considered candidates for ado-trastuzumab-emtansine
  • No metastatic sites >= 20 mm
  • Concurrent malignancy other than skin cancer
  • Inability to provide informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02226276

Locations
United States, California
City of Hope Medical Center Not yet recruiting
Duarte, California, United States, 91010
Contact: Joanne E. Mortimer, MD    800-826-4673    jmortimer@coh.org   
Principal Investigator: Joanne E. Mortimer, MD         
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Joanne Mortimer City of Hope Medical Center
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT02226276     History of Changes
Other Study ID Numbers: 14099, NCI-2014-01812, 14099
Study First Received: August 25, 2014
Last Updated: August 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasm Metastasis
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Neoplastic Processes
Pathologic Processes
Skin Diseases
Trastuzumab
Ado-trastuzumab emtansine
Maytansine
Copper
Fluorodeoxyglucose F18
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Radiopharmaceuticals
Diagnostic Uses of Chemicals
Molecular Mechanisms of Pharmacological Action
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on September 16, 2014